The Calcium Entry-Calcium Refilling Coupling

Abstract

Calcium ions (Ca²⁺) are versatile messengers that need to be tidily regulated in time and space in order to create a large number of signals. The coupling between Ca²⁺ entry and Ca²⁺ refilling is playing a central role in this Ca²⁺ homeostasis. Since the capacitative Ca²⁺ entry has been described, different mechanisms have been proposed in order to explain how the Ca²⁺ entry could be under control of intracellular store Ca²⁺ depletion. Today, in addition of STIM1 and Orai1, the two major elements of SOCe, increasing attention is put on the role of the transient receptor potential canonical (TRPC), that can form protein clusters with Orai1, and Sarco/endoplasmic reticulum Ca²⁺ATPases (SERCAs), that refill the stores and are also located in the same environment than SOC clusters. Altogether, these proteins elaborate either Ca²⁺ microdomains in the vicinity of the membrane or larger Ca²⁺ increases overtaking the whole cell. The coupling between Ca²⁺ entry and Ca²⁺ refilling can possibly act much further away from the plasma membrane. Ca²⁺, uptaken by SERCAs, have been described to move faster and further in the ER than in the cytosol and to create specific signal that depends on Ca²⁺ entry but at longer distance from it. The complexity of such created Ca²⁺ currents resides in the heteromeric nature of channels as well as the presence of different intracellular stores controlled by SERCA2b and SERCA3, respectively. A role for mitochondria has also been explored. To date, mitochondria are other crucial compartments that play an important role in Ca²⁺ homeostasis. Although mitochondria mostly interact with intracellular stores, coupling of Ca²⁺ entry and mitochondria cannot be completely rule out.